A drug combination aimed at preventing transmission of HIV from a pregnant woman to her fetus likely does not increase the risk for preterm birth and early infant death, according to a re-analysis of two studies funded by the National Institutes of Health. The research appears in the New England Journal of Medicine.

A previous study, called PROMISE or Promoting Maternal and Infant Survival Everywhere, compared the effectiveness of several drugs and treatment regimens prescribed to pregnant women with HIV in India and six African countries. It found that, compared to women on zidovudine-based therapy, women taking a combination treatment including the drug tenofovir disoproxil fumarate (TDF) were twice as likely to give birth to a very preterm infant and their infants were more likely to die within the first 14 days of life.

The authors of the current study wrote that the PROMISE results were surprising, given that earlier studies had found combinations containing TDF to be safe for use during pregnancy. The World Health Organization recommends that all adults with HIV, including pregnant women, receive a combination therapy that includes TDF.

The current analysis was led by Kathryn Rough, Sc.D., of the Harvard T.H. Chan School of Public Health and funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and National Institute of Allergy and Infectious Diseases. It compared the risk of preterm birth and other adverse birth outcomes from two studies of U.S. women: a trial from the Pediatric HIV/AIDS Cohort Study and a trial from the International Maternal Pediatric Adolescent AIDS Clinical Trial Network. The women in these studies received one of three combinations:

Zidovudine, lamivudine, lopinavir/ritonavir (ZDV/3TC/LPV/r)

DF, emtricitabine, lopinavir/ritonavir (TDF/FTC/LPV/r)

TDF, emtricitabine, atazanavir/ritonavir (TDF/FTC/ATV/r)

Researchers reviewed records of more than 4,600 infants born to 3,847 women. Of these, 954 women received ZDV/3TC/LPV/r, 128 women received TDF/FTC/LPV/r and 539 women received TDF/FTC/ATV/r. Their comparison of women receiving TDF/FTC/LPV/r to women receiving ZDV/3TC/LPV/r found no significant differences in the risk of preterm birth or low birth weight. Researchers also did not find any significant differences in severe birth outcomes, including very low birth weight, very preterm birth or infant death before 14 days after birth.

Notably, when researchers compared women treated with ZDV/3TC/LPV/r to women who received TDF/FTC/ATV/r, they found that the TDF group had a 10-percent-lower chance of preterm birth, low birth weight and infant death.

“The analysis provides reassurance that regimens containing TDF are appropriate for use during pregnancy,” said Rohan Hazra, M.D., chief of NICHD’s Maternal and Pediatric Infectious Disease Branch, which oversaw funding for the study.

About the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): NICHD conducts and supports research in the United States andthroughout the world on fetal, infant and child development; maternal, child and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visitwww.nichd.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation’s medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visitwww.nih.gov.